Specific Aims: l. To identify and characterize additional members of the Lrp regulon. 2. To determine whether there are lrp-like genes in organisms other than enteric bacteria that have a major global regulatory function. 3. To explore how Lrp activates transcription from the ilvIH promoter, and how leucine interferes with activation. 4. To investigate how leucine can overcome the effect of Lrp in some cases, potentiate the effect in other cases, and have no effect in yet other cases. 5. To determine the three dimensional structure of Lrp and of Lrp-DNA complexes. 6. To test the hypothesis that small changes in Lrp concentration underlie major changes in metabolism that occur in E. coli when cells make a transition from one medium to another.